General procedure for the synthesis of 4-fluoro-2-hydroxybenzonitrile from 2-methoxy-4-fluorobenzonitrile: A mixture of 4-fluoro-2-methoxybenzonitrile (4.53 g, 30 mmol) and aluminum trichloride (5.0 g, 37.6 mmol; purchased from Aldrich) in anhydrous toluene (30 mL) was stirred and reacted for 18 hours at 130 °C. After completion of the reaction, the mixture was cooled to room temperature, ice water (~50 mL) was added, and extracted with ether (20 mL × 2). The organic phases were combined, washed sequentially with water and saturated brine, and then dried with anhydrous magnesium sulfate. After concentration under reduced pressure, 4-fluoro-2-hydroxybenzonitrile (3.90 g, 28.5 mmol, 95% yield) was obtained as a white solid. Its structure was confirmed by the following characterization: 1H NMR (DMSO-d6, 300 MHz) δ ppm: 6.74-6.84 (2H, m, Ar-H), 7.71 (1H, dd, J = 7 Hz, J = 8.5 Hz, Ar-H), 11.64 (1H, s, OH); 13C NMR (DMSO-d6, 75.5 MHz) δ ppm: 95.13, 102.45, 102.78, 106.53, 106.83, 115.53, 134.68, 134.84, 161.41, 161.58, 163.00, 166.35. The calculated value of the high-resolution mass spectrometry (ESI-) for C7H3NOF (M-H) was 136.0199 and the measured value was 136.0199.
